EFFECT OF HYPERTHERMIA ON THE ANTIPROLIFERATIVE ACTIVITIES OF MURINE ALPHA-INTERFERON, INTERFERON-BETA, AND GAMMA-INTERFERON - DIFFERENTIAL ENHANCEMENT OF MURINE GAMMA-INTERFERON

  • 1 January 1986
    • journal article
    • research article
    • Vol. 46  (1) , 8-13
Abstract
Fever is frequently an important side effect of interferon (IFN) therapy. Studies have shown that culturing interferon-treated cells at elevated temperature heightens the antiproliferative activity of IFN-.alpha. and IFN-.beta.. Since IFN-.gamma. has also been shown to be a potent antiproliferative agent, the effect of elevated temperature on IFN-.gamma. activity was compared to its effect on IFN-.alpha. and IFN-.beta.. Mouse B-16 melanoma cells were simultaneously cultured under cloning conditions at a range of temperatures (37.3, 38.1, 38.6, and 39.4.degree. C) in the presence of MuIFN-.alpha., MuIFN-.beta., and MuIFN-.gamma.. The antiproliferative activities of all three interferons were enhanced by incubation at the elevated temperatures. However, the elevated temperatures had a more dramatic enhancing effect on the antiproliferative activity of MuIFN-.gamma. (10-fold enhancement) than of either MuIFN-.alpha. or MuIFN-.beta. (2.9- and 3.4-fold enhancement, respectively). Next, the enhancing effect of elevated temperature (39.4.degree. C) was examined for a range of interferon concentrations. The degree of the enhancing effect increased with increasing concentrations of MuIFN-.gamma. but not with increasing concentrations of MuIFN-.alpha. or MuIFN-.beta.. Enhancing effects of temperatures as high as 14-fold were observed for 100 units of MuIFN-.gamma./ml. This dramatic enhancement was observed for both natural and recombinant MuIFN-.gamma. and was neither a function of greater relative perception of MuIFN-.gamma. titer at elevated temperature nor a function of greater relative stability of MuIFN-.gamma. at the elevated temperature. The differential enhancement of MuIFN-.gamma. activity by elevated temperature appeared to be specific for the antiproliferative activity, since the antiviral activity of MuIFN-.gamma. was not relatively more enhanced at 39.4.degree. C than were the antiviral activities of MuIFN-.alpha. and MuIFN-.beta.. These results suggest that fever may be an important factor in maximizing the antitumor effects of MuIFN-.gamma. and perhaps of human IFN-.gamma.. They also raise the possibility that a combination treatment regimen of hyperthermia and interferon therapy, particularly IFN-.gamma. therapy, may provide a significant antitumor effect.